{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:44:45Z","timestamp":1790844285082,"version":"4.1.0"},"reference-count":106,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bruton's tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of B\u2010cell lymphoma (BCL). These drugs interfere with the mechanisms underlying malignant B\u2010cell pathophysiology, allowing better drug response as well as low toxicity. However, these multiple mechanisms also lead to drug resistance, which compromised the treatment outcome and needs to be solved urgently. This review focuses on genomic variations (such as\n                    <jats:italic>BTK<\/jats:italic>\n                    and its downstream\n                    <jats:italic>PCLG2<\/jats:italic>\n                    mutations as well as Del 8p, 2p+, Del 6q\/8p,\n                    <jats:italic>BIRC3<\/jats:italic>\n                    ,\n                    <jats:italic>TRAF2<\/jats:italic>\n                    ,\n                    <jats:italic>TRAF3<\/jats:italic>\n                    ,\n                    <jats:italic>CARD11<\/jats:italic>\n                    ,\n                    <jats:italic>MYD88<\/jats:italic>\n                    , and\n                    <jats:italic>CCND1<\/jats:italic>\n                    mutations) and related pathways (such as PI3K\/Akt\/mTOR, NF\u2010\u03baB, MAPK signaling pathways, overexpression of B\u2010cell lymphoma 6, platelet\u2010derived growth factor, toll\u2010like receptors, and microenvironment, cancer stem cells, and exosomes) involved in cancer pathophysiology to discuss the mechanisms underlying resistance to BTKi. We have also reviewed the newly reported drug resistance mechanisms and the proposed potential treatment strategies (the next\u2010generation BTKi, proteolysis\u2010targeting chimera\u2010BTK, XMU\u2010MP\u20103, PI3K\u2010Akt\u2010mTOR pathway, MYC or LYN kinase inhibitor, and other small\u2010molecule targeted drugs) to overcome drug resistance. The findings presented in this review lay a strong foundation for further research in this field.\n                  <\/jats:p>","DOI":"10.1002\/hon.2933","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T05:39:05Z","timestamp":1634708345000},"page":"605-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The resistance mechanisms and treatment strategies of BTK inhibitors in B\u2010cell lymphoma"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3948-2863","authenticated-orcid":false,"given":"Haoran","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Armed Police 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